Coenzyme Q10 Ubiquinone Deficiency Panel

Coenzyme Q10 (CoQ10) deficiency is associated with three major forms of clinical phenotypes: a predominantly myopathic form with central nervous system involvement, an infantile encephalomyopathy with renal dysfunction (steroid-resistant nephrotic syndrome), and an ataxic form with cerebellar atrophy (Desbats et al. 2015; Quinzii et al. 2006). Age of onset is variable from birth to the seventh decade. Accurate molecular diagnosis of Coenzyme Q10 deficiency is important for treatment.

Coenzyme Q10 is an essential component of the mitochondrial respiratory chain and an antioxidant. Coenzyme Q10 deficiency is a group of autosomal recessive disorders (Desbats et al. 2015; Yubero et al. 2015). It can be caused by defects in the genes directly involved in the biosynthesis of Coenzyme Q10 (primary deficiency) or unrelated to Coenzyme Q10 biosynthesis (secondary deficiency) as listed below. The spectrum of pathogenic variants throughout these genes includes all types of changes (Human Gene Mutation Database).

Primary Coenzyme Q10 deficiency: PDSS1, PDSS2, COQ2, COQ4, COQ6, COQ9, ADCK3/COQ8A, and ADCK4/COQ8B

Secondary Coenzyme Q10 deficiency: APTX, ETFDH, ETFA, and ETFB

See individual gene test descriptions for more information on molecular biology of gene products.

Screenings for pathogenic variants in the associated genes in a large cohort of patients with Coenzyme Q10 deficiency have not been reported. To date, studies have focused on individual genes in a limited number of families. Therefore, mutation detection rate of this panel is unknown.

Large deletions and/or duplications have been documented in the Human Gene Mutation Database (HGMD) in the following genes, but are relatively uncommon: ADCK3/COQ8A, COQ4, ETFDH, ETFA, and APTX.

No large deletions or duplications have been reported in the other 7 genes of the current panel.

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.6% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).